22 research outputs found

    Novel Domain Wall and Minkowski Vacua of D=9 Maximal SO(2) Gauged Supergravity

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    We show that a generalised reduction of D=10 IIB supergravity leads, in a certain limit, to a maximally extended SO(2) gauged supergravity in D=9. We show the scalar potential of this model allows both Minkowski and a new type of domain wall solution to the Bogomol'nyi equations. We relate these vacua to type IIB D-branes.Comment: 28 pages, 1 figure, Latex2

    Effective Field Theories and Inflation

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    We investigate the possible influence of very-high-energy physics on inflationary predictions focussing on whether effective field theories can allow effects which are parametrically larger than order H^2/M^2, where M is the scale of heavy physics and H is the Hubble scale at horizon exit. By investigating supersymmetric hybrid inflation models, we show that decoupling does not preclude heavy-physics having effects for the CMB with observable size even if H^2/M^2 << O(1%), although their presence can only be inferred from observations given some a priori assumptions about the inflationary mechanism. Our analysis differs from the results of hep-th/0210233, in which other kinds of heavy-physics effects were found which could alter inflationary predictions for CMB fluctuations, inasmuch as the heavy-physics can be integrated out here to produce an effective field theory description of low-energy physics. We argue, as in hep-th/0210233, that the potential presence of heavy-physics effects in the CMB does not alter the predictions of inflation for generic models, but does make the search for deviations from standard predictions worthwhile.Comment: 19 pages, LaTeX, no figures, uses JHEP

    Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A

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    AbstractBackground: The CDKN2/INK4A tumour suppressor gene is deleted or mutated in a large number of human cancers. Overexpression of its product, p16, has been shown to block the transition through the G1/S phase of the cell cycle in a pRb-dependent fashion by inhibiting the cyclin D-dependent kinases cdk4 and cdk6. Reconstitution of p16 function in transformed cells is therefore an attractive target for anti-cancer drug design.Results We have identified a 20-residue synthetic peptide — corresponding to amino acids 84–103 of p16 – that interacts with cdk4 and cdk6, and inhibits the in vitro phosphorylation of pRb mediated by cdk4–cyclin D1. The amino-acid residues of p16 important for its interaction with cdk4 and cdk6 and for the inhibition of pRb phosphorylation were defined by an alanine substitution series of peptides. In normal proliferating human HaCaT cells and in cells released from serum starvation, entry into S phase was blocked by the p16-derived peptide when it was coupled to a small peptide carrier molecule and applied directly to the tissue culture medium. This cell-cycle block was associated with an inhibition of pRb phosphorylation in vivo.Conclusion These results demonstrate that a p16-derived peptide can mediate three of the known functions of p16: firstly, it interacts with cdk4 and cdk6; secondly, it inhibits pRb phosphorylation in vitro and in vivo; and thirdly, it blocks entry into S phase. The fact that one small synthetic peptide can enter the cells directly from the tissue culture medium to inhibit pRb phosphorylation and block cell-cycle progression makes this an attractive approach for future peptidometic drug design. Our results suggest a novel and exciting means by which the function of the p16 suppressor gene can be restored in human tumours

    Gender aspects in allergies of pets – A secondary publication and update

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    Allergies need not only affect humans; this multifactorial and complex disease can also affect animals. Comparative allergology investigates the many similarities between the pathogenesis, clinics, diagnosis, and therapy of the disorders in humans and pet animals. In contrast to human allergy research, the veterinary field lacks access to a central database, which means there are no cohort studies published. This limits not only the research on breed and regional differences in allergies, but also further studies on the impact of gender in allergies of domestic animals. Moreover, domestic cats, dogs and male horses are castrated in most cases, which neutralises any effects of sexual hormones. In this review article a few interesting findings regarding gender aspects in companion animals were extracted from current literature. In summary, there is a lack of data on gender effects on allergies in cats, dogs or horses. Keywords: Atopic dermatitis, Canine, Cat, Dog, Gender, Horse, Pe

    Innate function of house dust mite allergens: robust enzymatic degradation of extracellular matrix at elevated pH

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    Background Exposure to the house dust mite Dermatophagoides pteronyssinus (D.p.) increases the risk for developing allergic diseases in humans and their best friends, the dogs. Here, we explored whether this allergenic mite via its enzymes may impact the cutaneous extracellular matrix (ECM), which critically determines epithelial barrier integrity both structurally and functionally.Methods Two extracts obtained from either dust-purified or cultured D.p. bodies were used in the present study. To assess the potential impact of D.p. on protein components of the ECM, proteolytic activity of the D.p. extracts were determined by casein and gelatin gel zymography, and their N-acetyl-β-hexosaminidase activity determined colorimetrically. In addition, IgE-dependent and innate degranulation potential of D.p. was examined in canine MPT-1 mast cells and neurite outgrowth assay using rat pheochromocytoma PC-12 cells.Results In gel zymography, both extracts digested the substrates casein and gelatin in a dose-dependent manner, especially at alkaline pH, and effective in a wide range of temperatures (30 °C−42 °C). In particular, a 25-kDa band corresponding to Der p 1, the major D.p. allergen for humans, was found enzymatically active in both casein and gelatin gels regardless of the presence of metal ions and of alkaline conditions. Besides protease activity, N-acetyl-β-hexosaminidase activity was detected in both extracts, suggesting that D.p. affects the cutaneous ECM through deteriorating both proteins and glycosaminoglycans. While both D.p. extracts induced IgE-dependent mast cell degranulation, much less innate effects on mast- and neuronal cells were observed.Conclusions Our data highlight that D.p. is a robust source of several distinct enzymes with protease- and N-acetyl-β-hexosaminidase activities. In alkaline milieu they can degrade components of the ECM. Therefore, D.p. may contribute to epithelial barrier disruption especially when the skin surface pH is elevated. Keywords: Dermatophagoides pteronyssinus, Allergens, Epithelial barrier, Extracellular matrix, Proteases, N-acetyl-β-hexosaminidas

    Edible insects: Cross-recognition of IgE from crustacean- and house dust mite allergic patients, and reduction of allergenicity by food processing

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    Background: Insects have become increasingly interesting as alternative nutrient sources for feeding humans and animals, most reasonably in processed form. Initially, some safety aspects — among them allergenicity — need to be addressed. Objective: To reveal the cross-reactivity of shrimp-, mite- and flies-allergic patients to different edible insects, and further to assess the efficacy of food processing in reducing the recognition of insect proteins by patients' IgE and in skin prick testing of shrimp-allergic patients. Methods: IgE from patients allergic to crustaceans, house dust mite or flies was evaluated for cross-recognition of proteins in house cricket Acheta domesticus (AD), desert locust Schistocerca gregaria (SG) and Yellow mealworm Tenebrio molitor (TM). Changes in IgE-binding and SPT-reactivity to processed insect extracts were determined for migratory locust (Locusta migratoria, LM), after different extraction methods, enzymatic hydrolysis, and thermal processing were applied. Results: IgE from patients with crustacean-allergy shows cross-recognition of AD, SG and stable flies; house dust mite allergics' IgE binds to AD and SG; and the flies-allergic patient recognized cricket, desert locust and migratory locust. Cross-reactivity and allergenicity in SPT to LM can be deleted by conventional processing steps, such as hydrolysis with different enzymes or heat treatment, during the preparation of protein concentrates. Conclusion: The results show that crustacean-, HDM- and stable flies-allergic patients cross-recognize desert locust and house cricket proteins, and crustacean-allergic patients also flies proteins. Furthermore, this study shows that appropriate food processing methods can reduce the risk of cross-reactivity and allergenicity of edible insects. Keywords: Allergenicity, Cross-recognition, Edible insects, Enzymatic hydrolysis, Food allergy, Immunoreactivity, Thermal processin
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